title: A randomized, double-blind, placebo-controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson's disease (the ADAGIO study): rationale, design, and baseline characteristics.
abstract: A neuroprotective therapy is the single most important unmet medical need in Parkinson's disease. Several promising agents in the laboratory have been tested in the clinic, but none has been established in clinical trials to have a disease modifying effect despite positive results because of potential confounding symptomatic or pharmacologic effects. The delayed start design was developed to try to avoid a symptomatic confound when testing a putative neuroprotective therapy. In this study design, patients are randomly assigned to study drug or placebo in the first phase of the study, and both groups receive the active drug in the second phase. If benefits seen at the end of phase I persist through the end of phase II, they cannot be readily explained by a symptomatic effect (as patients in both groups are receiving the same medication) and benefits in the early start group must relate to the early initiation of the treatment. Although the precise mechanism responsible for such an effect can be debated, positive results in a delayed start study indicate that patients who receive early treatment have a better outcome than those where the treatment is delayed. We are using the delayed start design to assess the potential disease modifying effects of rasagiline in a prospective double blind controlled trial (the ADAGIO study). We here describe the rationale for the study and baseline characteristics of the 1,176 patients who have been enrolled into the trial.
authors.affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029, USA. warren.olanow@mssm.edu
authors.forename: C Warren
authors.initials: CW
authors.lastname: Olanow
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.forename: Joseph
authors.initials: J
authors.lastname: Jankovic
authors.forename: William
authors.initials: W
authors.lastname: Langston
authors.forename: Anthony
authors.initials: A
authors.lastname: Lang
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Stocchi
authors.forename: Eldad
authors.initials: E
authors.lastname: Melamed
authors.forename: Eli
authors.initials: E
authors.lastname: Eyal
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D007189:Indans; D018696:Neuroprotective Agents; C031967:rasagiline